Dual activities of lysis and capsule degradation enable the bacteriophage protein Lys33795 to effectively disrupt Streptococcus suis biofilms
- 1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
- 2Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China
- 3Yunnan Provincial Key Laboratory of Zoonosis Control and Prevention, Yunnan Institute of Endemic Diseases Control and Prevention, Kunming, China
Abstract
Streptococcus suis (S. suis) is an encapsulated zoonotic pathogen that can form recalcitrant biofilms. Bacteriophage-derived endolysins and depolymerases represent promising antibiofilm agents, but currently, no report has described protein which displays both of lytic and capsule degradation activities simultaneously. Here, we mined the porcine gut virome and identified Lys33795, a dual-activity antibacterial protein that degrades both capsule and peptidoglycan of S. suis. Lys33795 consists of an N-terminal GH25_muramidase domain and a C-terminal cell wall binding domain (CBD). However, translational reinitiation at an internal start codon (M217) in the Lys33795 sequence generates an additional CBD that may assembles with the full-length protein to form an oligomeric complex. Interestingly, the GH25 muramidase truncation fragment of Lys33795 not only retains its classical function as a peptidoglycan hydrolase for degrading bacterial cell walls but also exhibits degradation activity towards capsule. This discovery contrasts sharply with the traditional functional understanding of the GH25 family. In addition, the CBD alone has a stable dimer and, as a nonstandard depolymerase without any classical polysaccharide-degrading catalytic domains, retains its degradation activity against S. suis capsule. We elucidated the molecular mechanism of Lys33795 exhibiting dual activity by combining mutagenesis, lysis, and capsule degradation activity assays. In addition, the results of in vitro and in vivo experiments showed that Lys33795 can effectively prevent and clear S. suis biofilms, and is more effective than single active mutants, and has a enhance effect when used in combination with antibiotics. This study describes the first multimeric bacteriophage protein with dual activities of lysis and capsule degradation against S. suis, encoded by a single gene. These findings provide valuable insights for designing potent antibacterial proteins targeting encapsulated pathogens. Author summary: Some pathogenic bacteria are protected by their surface capsules and can form a sticky biofilm as a shelter, preventing being eliminated by antibiotics and other drugs. S. suis is such a zoonotic pathogen. In this study, we discovered a novel bacteriophage antimicrobial protein Lys33795, whose multimeric structure is encoded by a single gene and possesses the dual degradation function of capsule and cell wall peptidoglycan. Such a dual-functional antimicrobial protein has never been observed before. Interestingly, both of the separate GH25_muramidase domain and the separate CBD of Lys33795 exhibit degradation activity towards capsule, which is in stark contrast to the traditional functions understanding of the GH25 family and CBD domain. The experimental results showed that this protein could kill various serotypes of S. suis. Whether it is preventing biofilm formation or clearing existing biofilms, its performance is superior to that of single lytic or capsule degradation activity mutant protein. This discovery provides a new approach for developing novel antibacterial drugs and also provides new insights for the prevention and control of other capsular Gram-positive bacteria.
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BibTeX
@article{ji2026dual,
title = {{Dual activities of lysis and capsule degradation enable the bacteriophage protein Lys33795 to effectively disrupt Streptococcus suis biofilms}},
author = {Yalu Ji and Meimei Zhang and Liran Song and Hui Ning and Li Wang and Cao Qiu and Jingmin Gu},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014741},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014741},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual activities of lysis and capsule degradation enable the bacteriophage protein Lys33795 to effectively disrupt Streptococcus suis biofilms
AU - Yalu Ji
AU - Meimei Zhang
AU - Liran Song
AU - Hui Ning
AU - Li Wang
AU - Cao Qiu
AU - Jingmin Gu
PY - 2026
DA - 2026/10/23
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014741
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014741
AB - Streptococcus suis (S. suis) is an encapsulated zoonotic pathogen that can form recalcitrant biofilms. Bacteriophage-derived endolysins and depolymerases represent promising antibiofilm agents, but currently, no report has described protein which displays both of lytic and capsule degradation activities simultaneously. Here, we mined the porcine gut virome and identified Lys33795, a dual-activity antibacterial protein that degrades both capsule and peptidoglycan of S. suis. Lys33795 consists of an N-terminal GH25_muramidase domain and a C-terminal cell wall binding domain (CBD). However, translational reinitiation at an internal start codon (M217) in the Lys33795 sequence generates an additional CBD that may assembles with the full-length protein to form an oligomeric complex. Interestingly, the GH25 muramidase truncation fragment of Lys33795 not only retains its classical function as a peptidoglycan hydrolase for degrading bacterial cell walls but also exhibits degradation activity towards capsule. This discovery contrasts sharply with the traditional functional understanding of the GH25 family. In addition, the CBD alone has a stable dimer and, as a nonstandard depolymerase without any classical polysaccharide-degrading catalytic domains, retains its degradation activity against S. suis capsule. We elucidated the molecular mechanism of Lys33795 exhibiting dual activity by combining mutagenesis, lysis, and capsule degradation activity assays. In addition, the results of in vitro and in vivo experiments showed that Lys33795 can effectively prevent and clear S. suis biofilms, and is more effective than single active mutants, and has a enhance effect when used in combination with antibiotics. This study describes the first multimeric bacteriophage protein with dual activities of lysis and capsule degradation against S. suis, encoded by a single gene. These findings provide valuable insights for designing potent antibacterial proteins targeting encapsulated pathogens. Author summary: Some pathogenic bacteria are protected by their surface capsules and can form a sticky biofilm as a shelter, preventing being eliminated by antibiotics and other drugs. S. suis is such a zoonotic pathogen. In this study, we discovered a novel bacteriophage antimicrobial protein Lys33795, whose multimeric structure is encoded by a single gene and possesses the dual degradation function of capsule and cell wall peptidoglycan. Such a dual-functional antimicrobial protein has never been observed before. Interestingly, both of the separate GH25_muramidase domain and the separate CBD of Lys33795 exhibit degradation activity towards capsule, which is in stark contrast to the traditional functions understanding of the GH25 family and CBD domain. The experimental results showed that this protein could kill various serotypes of S. suis. Whether it is preventing biofilm formation or clearing existing biofilms, its performance is superior to that of single lytic or capsule degradation activity mutant protein. This discovery provides a new approach for developing novel antibacterial drugs and also provides new insights for the prevention and control of other capsular Gram-positive bacteria.
SN - 1553-7374
SN - 1553-7366
ER -